The invention relates to mass spectrometers, and more particularly to mass spectrometers which modulate sample collision energy.
Mass spectrometry techniques can involve the detection of ions that have undergone physical changes in a mass spectrometer. Frequently, the physical change involves fragmenting a selected precursor (or “parent”) ion and recording the mass spectrum of the resultant fragment ions. The information in the fragment ion mass spectrum is often a useful aid in elucidating the structure of the precursor ion. The general approach used to obtain a mass spectrometry/mass spectrometry (MS/MS or MS2) spectrum is to isolate a selected precursor ion with a suitable mass-charge (m/z) analyzer, and to subject the precursor ion to energetic collisions with a neutral gas in order to analyze the mass of the resulting fragment ions in order to generate a mass spectrum.
Triple quadrupole mass spectrometers (TQMSs) perform MS/MS analyses through the use of two quadrupole mass analyzers separated by a pressurized reaction region, sometimes called a collision cell, for the fragmentation step. For a sample mixture, the first quadrupole mass analyzer selectively transmits ions of interest, or precursor ions, into a collision cell containing an inert background gas. Fragments are produced through collision-induced dissociation (CID) upon collision with the neutral gas atoms or molecules. The fragments are then transmitted and mass-analyzed in a third quadrupole mass analyzer. Chemical information, including the structure of the precursor ion, can be derived from these fragments.
Quadrupole-time of flight (QqTOF) mass spectrometers typically employ time-of-flight (TOF) mass analyzers in place of the third quadrupole sets used in TQMS systems. Use of TOF analyzers in MS/MS techniques provides improved capabilities where wide-range, rapidly repeated scans are desired. TOF analyzers can enable, for example, full scan data to be acquired over a wide range of m/z ratios, each scan being completed in sub-millisecond time frames. This is particularly advantageous in that thousands of scans may be desired in accumulating a single mass spectrum.
The nature of fragmentation within a collision cell of a precursor ion selected from a mass analyzer is dependent upon the collision energy (CE) experienced by the precursor ion within the collision cell. The CE (which is sometimes also referred to as the fragmentation energy) is a function of factors which include the momentum, or injection energy, that the ion possesses upon entering the collision cell, and/or which is imparted to the ion while it is within the collision cell, and the pressure of any gas(ses) provided within the collision cell.
In order to obtain more information from a precursor ion, an additional stage of MS can be applied to the MS/MS schemes outlined above, resulting in MS/MS/MS, or MS3. For example, the collision cell may be operated as an ion trap, wherein fragment ions are resonantly excited to promote further CID. See, for example, WO 00/33350, published 8 Jun. 2000 in the name of Douglas et al. In that case, the third quadrupole of a TQMS device functions as a mass analyzer to record the resulting fragmentation spectrum.
In MS2 and MS3 techniques, the optimal collision energy may be selected based on the charge state and mass of the precursor ion. See, for example, Haller et al., J. Am. Soc. Mass Spectrom. 1996, 7, 677-681, the entire contents of which are incorporated by this reference. Although this information is theoretically known, however, in practice it can be difficult to approximate the optimum collision energy, and several attempts are often necessary to produce a useful spectrum, at the expense of time and samples. For example, the use of a non-optimal collision energy can result in over- or under-fragmentation of the precursor ion and significant reduction in the quantity and quality of the structural information available. The retention of the precursor ion in the resultant spectrum can be useful for providing a reference ion for determining the extent of fragmentation.
An alternative approach to obtaining improved ion fragmentation spectra is described in US 2004/0041090, published 4 Mar. 2004 in the name of Bloomfield, et al.